A new treatment for breast cancer using a combination of two drugs: AZD9496 and palbociclib

Sci Rep. 2024 Jan 15;14(1):1307. doi: 10.1038/s41598-023-48305-z.

Abstract

In this study, we examined a mathematical model of breast cancer (BC) treatment that combines an oral oestrogen receptor inhibitor, AZD9496 with Palbociclib, a selective inhibitor of cyclin- dependent kinases CDK4 and CDK6. Treatment is described by analytical functions that enable us to control the dosage and time interval of the treatment, thus personalising the treatment for each patient. Initially, we investigated the effect of each treatment separately, and finally, we investigated the combination of both treatments. By applying numerical simulations, we confirmed that the combination of AZD9496 with palbociclib was the optimal treatment for BC. The dosage of AZD9496 increased and decreased throughout the treatment period, while the intervals were constant between treatments. Palbociclib changed almost cyclically, whereas the time intervals remained constant. To investigate the mathematical model, we applied the singularly perturbed homotopy analysis method, which is a numerical algorithm. The significant advantage of this method is that the mathematical model does not have to contain a small parameter (as is standard in perturbation theory). However, it is possible to artificially introduce a small parameter into the system of equations, making it possible to study the model using asymptotic methods.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Cinnamates*
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Female
  • Humans
  • Indoles*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use

Substances

  • palbociclib
  • AZD9496
  • Pyridines
  • Piperazines
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Protein Kinase Inhibitors
  • Cinnamates
  • Indoles